Exploring the impacts of risk factors on mortality patterns of global Alzheimer's disease and related dementias from 1990 to 2021.

Alzheimer's Disease and Related Dementias (ADRD) affect millions of people worldwide, with mortality rates influenced by several risk factors and exhibiting significant heterogeneity across geographical regions. This study aimed to investigate the impact of risk factors on global ADRD mortality patterns from 1990 to 2021, utilizing clustering and modeling techniques. Data on ADRD mortality rates, cardiovascular disease, and diabetes prevalence were obtained for 204 countries from the GBD platform. Additional variables such as HDI, life expectancy, alcohol consumption, and tobacco use prevalence were sourced from the UNDP and WHO. All the data were extracted for men, women, and the overall population. Longitudinal k-means clustering and generalized estimating equations were applied for data analysis. The findings revealed that cardiovascular disease had significant positive effects of 1.84, 3.94, and 4.70 on men, women, and the overall ADRD mortality rates, respectively. Tobacco showed positive effects of 0.92, 0.13, and 0.39, while alcohol consumption had negative effects of - 0.59, - 9.92, and - 2.32, on men, women, and the overall ADRD mortality rates, respectively. The countries were classified into five distinct subgroups. Overall, cardiovascular disease and tobacco use were associated with increased ADRD mortality rates, while moderate alcohol consumption exhibited a protective effect. Notably, tobacco use showed a protective effect in cluster A, as did alcohol consumption in cluster B. The effects of risk factors on ADRD mortality rates varied among the clusters, highlighting the need for further investigation into the underlying causal factors.

The Relation of Serum Vitamin C Concentrations with Alzheimer's Disease Mortality in a National Cohort of Community-Dwelling Elderly Adults.

The relation of vitamin C with Alzheimer's disease (AD) is equivocal. The aim of this study was to assess the relation of serum vitamin C levels with AD-related mortality, and to evaluate the threshold beyond which the potential benefits of higher serum concentrations of vitamin C for AD mortality ceases. The cohort consisted of 4504 adults aged ≥60 years enrolled in the National Health and Nutrition Examination Survey who had serum measures of vitamin C and no cognitive impairment at baseline (1988-1994) and were followed-up for mortality until 2019. Vitamin C was assayed from fasting blood samples using isocratic high-performance liquid chromatography. At baseline, the mean age of participants was 70 years, with 42.7% being men. At the end of follow-up (median: 15 years), the AD mortality rate was 2.4 per 1000 person-years. In the Cox regression models, compared to participants in the lowest tertile of serum vitamin C (<0.56 mg/dL), those in the highest tertile (>0.98 mg/dL) had a lower risk of AD mortality (hazard ratio: 0.44, 95% confidence intervals: 0.25-0.77) after adjusting for sociodemographic factors, behavior/lifestyle factors, prevalent health conditions, and dietary vitamin C intake. In dose-response analysis using restricted cubic splines, vitamin C concentrations beyond 2.3 mg/dL were associated with the elevated risk of AD-related mortality. The findings from this national sample of community-dwelling elderly adults suggest that higher levels of serum vitamin C are associated with slower AD disease progression, although levels beyond the normal reference values were associated with a higher risk of AD mortality.

Prediction of disease-free survival for precision medicine using cooperative learning on multi-omic data.

In precision medicine, both predicting the disease susceptibility of an individual and forecasting its disease-free survival are areas of key research. Besides the classical epidemiological predictor variables, data from multiple (omic) platforms are increasingly available. To integrate this wealth of information, we propose new methodology to combine both cooperative learning, a recent approach to leverage the predictive power of several datasets, and polygenic hazard score models. Polygenic hazard score models provide a practitioner with a more differentiated view of the predicted disease-free survival than the one given by merely a point estimate, for instance computed with a polygenic risk score. Our aim is to leverage the advantages of cooperative learning for the computation of polygenic hazard score models via Cox's proportional hazard model, thereby improving the prediction of the disease-free survival. In our experimental study, we apply our methodology to forecast the disease-free survival for Alzheimer's disease (AD) using three layers of data. One layer contains epidemiological variables such as sex, APOE (apolipoprotein E, a genetic risk factor for AD) status and 10 leading principal components. Another layer contains selected genomic loci, and the last layer contains methylation data for selected CpG sites. We demonstrate that the survival curves computed via cooperative learning yield an AUC of around $0.7$, above the state-of-the-art performance of its competitors. Importantly, the proposed methodology returns (1) a linear score that can be easily interpreted (in contrast to machine learning approaches), and (2) a weighting of the predictive power of the involved data layers, allowing for an assessment of the importance of each omic (or other) platform. Similarly to polygenic hazard score models, our methodology also allows one to compute individual survival curves for each patient.

Fish and Shellfish Consumption, Cognitive Health and Mortality from Alzheimer's Disease among US Adults Aged 60 and Older.

BACKGROUND: Relationships of fish-shellfish consumption, cognitive health and mortality from Alzheimer's disease (AD) among US adults aged 60 years and older have not been adequately studied. OBJECTIVES: To determine the relationship of fish-shellfish consumption, cognitive health and mortality from AD in US adults aged 60 years and older. DESIGN, SETTING AND PARTICIPANTS: The data of this cross-sectional study of US adults aged 60 years and older were from the National Nutrition and Health Examination Survey (NHANES) datasets. Frequency of fish-shellfish consumption, its association with subjective cognitive decline (SCD) and AD mortality of these participants between 1999 and 2018 and cognitive assessment scores between 2011 and 2014 were analyzed. MEASUREMENTS AND RESULTS: US adults aged 60 years and older consumed fish-shellfish 1.2 times/week and had a blood Hg of 1.63 ug/L on average between 1999 and 2018. Participants aged 60 years and older in the highest quartile of fish-shellfish consumption (~3 times/week) had significantly higher cognitive assessment scores than those in the lowest quartile (rare or no fish-shellfish consumption). Adults in the highest quartile of fish-shellfish consumption had a 30% lower risk (odds ratio 0.7, 95%CI 0.57-0.87) of SCD, and 44% lower risk (hazard ratio 0.56, 95%CI 0.35-0.9) of AD mortality than those in the lowest quartile. CONCLUSION: Increased fish-shellfish consumption was associated with improved scores of cognitive assessment and reduced risks of SCD and AD mortality.

Interrelationship of Sleep Disturbances and Cognitive Status on Mortality.

Sleep disturbances may promote the development and advancement of Alzheimer's disease. Our purpose was to determine if sleep disturbances were associated with earlier mortality while accounting for cognition. The National Alzheimer's Coordinating Center database was used to evaluate mortality risk conferred by sleep, and the Montreal Cognitive Assessment score determined cognitive status. Demographics, sleep disturbances, cognitive status, and comorbid/other neuropsychiatric conditions were examined as predictors of survival time via Cox regression. The sample (N = 31,110) had a median age [interquartile range] of 72 [66, 79] years, MoCA score of 23 [16, 26], and survival time of 106.0 months [104.0,108.0]; 10,278 (33%) died during follow-up; 21% (n = 6461) experienced sleep disturbances. Sleep disturbances impacted survival time depending on cognition, with the greatest effect in transition from normal to cognitive impairment (P < .001). Findings support that sleep disturbances negatively impact survival time, and the impact of sleep disturbances on survival time is interrelated with cognition.

Variability in Alzheimer's disease mortality from European vital statistics, 2012-2020.

OBJECTIVE: Data regarding the trends in Alzheimer's disease (AD) mortality in the modern European Union (EU-27) member states are lacking. We assess the sex- and age-specific trends in AD mortality in the EU-27 member states between years 2012 and 2020. METHODS: Data on cause-specific deaths and population numbers by sex for each country of the EU-27 were retrieved through publicly available European Statistical Office (EUROSTAT) dataset from 2012 to 2020. AD-related deaths were ascertained when the ICD-10 code G30 was listed as the primary cause of death in the medical death certificate. To calculate annual trends, we assessed the average annual percent change (AAPC) with relative 95% confidence intervals (CIs) using Joinpoint regression. RESULTS: During the study period, 751,493 deaths (1.7%, 233,271 males and 518,222 females) occurred in the EU-27 because of AD. Trends in the proportion of AD-related deaths per 1000 total deaths slightly increased from 16.8% to 17.5% (p for trend <0.001). The age-adjusted mortality rate was higher in women over the entire study period. Joinpoint regression analysis revealed a stagnation in age-adjusted AD-related mortality from 2012 to 2020 among EU-27 Member States (AAMR: -0.1% [95% CI: -1.8-1.79], p = 0.94). Stratification by Country showed relevant regional disparities, especially in the Northern and Eastern EU-27 member states. CONCLUSIONS: Over the last decade, the age-adjusted AD-related mortality rate has plateaued in EU-27. Important disparities still exist between Western and Eastern European countries.

A Dementia mortality rates dataset in Italy (2012-2019).

Dementia is on the rise in the world population and has been defined by the World Health Organization as a global public health priority. In Italy, according to demographic projections, in 2051 there will be 280 elderly people for every 100 young people, with an increase in all age-related chronic diseases, including dementia. Currently the total number of patients with dementia is estimated to be over 1 million (mainly with Alzheimer's disease (AD) and Parkinson's disease (PD)). In-depth studies of the etiology and physiology of dementia are complicated due to the complexity of these diseases and their long duration. In this work we present a dataset on mortality rates (in the form of Standardized Mortality Ratios, SMR) for AD e PD in Italy at provincial level over a period of 8 years (2012-2019). Access to long-term, spatially detailed and ready-to-use data could favor both health monitoring and the research of new treatments and new drugs as well as innovative methodologies for early diagnosis of dementia.

Area-Level Infant Mortality Exposure in Early Life and Alzheimer's Disease Mortality: Examining Variation Based on Age, Sex, and Place of Birth.

BACKGROUND: Growing evidence suggests that critical periods in early life may contribute to one's risk of Alzheimer's disease and related dementias (ADRD) in later life. In this paper we explore the role that exposure to infant mortality plays in later life ADRD. OBJECTIVE: To determine if exposure to early life infant mortality is associated with later mortality from ADRD. Also, we explore how these associations differ by sex and age group, along with the role of state of birth and competing risks of death. METHODS: We use a sample of over 400,000 individuals aged 50 and above with the NIH-AARP Diet and Health Study with mortality follow-up, allowing us to examine how early life infant mortality rates along with other risk factors play in one's individual mortality risk. RESULTS: We show that infant mortality rates are associated with death from ADRD among those under 65 years of age, but not those over 65 at baseline interview. Moreover, when factoring in competing risks of death, the associations are relatively unchanged. CONCLUSION: These results suggest that those exposed to worse adverse conditions during critical periods increase their likelihood of death from ADRD earlier than average, due to that exposure increasing their susceptibility to develop illness later on in life.

Trends in Alzheimer Disease Mortality Among American Indian and Alaska Native People Between 2011 and 2019.

PURPOSE: The number of American Indian and Alaska Native (AI/AN) people living with dementia is expected to increase 5-fold by 2060. Social determinants of health may explain disparities in the incidence of Alzheimer disease (AD) but remain largely overlooked. METHODS: We examined the time trend of AD mortality rates and associations of the percentage of AI/ANs, density of primary care physicians and neurologists, area deprivation index, rurality, and Indian Health Service region with AD mortality in 646 purchased/referred care delivery area counties. RESULTS: AD mortality rates significantly increased over time. Counties with higher concentrations of AI/AN people had lower AD mortality. More deprived counties had 34% higher AD mortality compared with less deprived counties. AD mortality was 20% lower in nonmetro counties than in metro counties. CONCLUSIONS: Findings have implications for prioritizing areas where more resources for AD care, education, or outreach are needed.

Spatial disparity and factors associated with dementia mortality: A cross-sectional study in Zhejiang Province, China.

Objective: Evidence of spatial disparity in dementia mortality in China has been found to have higher dementia mortality in eastern and rural China. Regional factors of physical and social features may be influencing this spatial disparity. However, the extent of spatial difference in dementia mortality across small regional localities is unclear. This study aims to investigate the geographic variations in mortality and risk of all dementia subtypes and identify the effect of the associated environmental risk factors. Methods: We used surveillance data on death reports from Alzheimer's disease and other forms of dementia in Zhejiang province from 2015 to 2019. We estimated the relative risk of dementia mortality using a Bayesian spatial model. We mapped predicted relative risk to visualize the risk of death from different types of dementia and to identify risk factors associated with dementia. Results: Thirty thousand three hundred and ninety-eight deaths attributable to dementia as the underlying or related cause (multiple causes) were reported during 2015-2019. Counties and districts in the southeast and west of Zhejiang province had significantly higher standardized mortality ratios than others. Counties and districts with a smaller proportion of residents aged 60 years or older, poorer economic status, insufficient health resources, and worse pollution had a higher risk of deaths due to dementia. Conclusion: Higher risks of dementia mortality were found in counties and districts with poorer economic status, insufficient health resources, and worse pollution in Zhejiang. Our study adds new evidence on the association between socioeconomic and environmental factors and the mortality risk due to dementia.

Report on trial death stokes Alzheimer's drug fears.

Amyloid-clearing antibody lecanemab faces key FDA hearing in June.

Mortality Risks and Causes of Death by Dementia Types in a Japanese Cohort with Dementia: NCGG-STORIES.

BACKGROUND: Prognosis-related information regarding dementia needs to be updated, as changes in medical and long-term care environments for patients with dementia in recent decades may be improving the prognosis of the disease. OBJECTIVE: We aimed to investigate the mortality, cause of death, and prognostic factors by types of dementia in a Japanese clinic-based cohort. METHODS: The National Center for Geriatrics and Gerontology-Life Stories of People with Dementia consists of clinical records and prognostic data of patients who visited the Memory Clinic in Japan. Patients who attended the clinic between July 2010 and September 2018, or their close relatives, were asked about death information via a postal survey. A cohort of 3,229 patients (mean age, 76.9; female, 1,953) was classified into six groups: normal cognition (NC), mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia, dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration. A Cox proportional hazards model was employed to compare the mortality of each type of dementia, MCI, and NC. RESULTS: Patients with all types of dementia and MCI had higher mortality rates than those with NC (hazard risks: 2.61-5.20). The most common cause of death was pneumonia, followed by cancer. In the MCI, AD, and DLB groups, older age, male sex, and low cognitive function were common prognostic factors but not presence of apolipoprotein E ɛ4 allele. CONCLUSION: Our findings suggest important differences in the mortality risk and cause of death among patients with dementia, which will be useful in advanced care planning and policymaking.

Tendência de mortalidade por doença de Alzheimer no Brasil, 2000 a 2019 / Tendencias de mortalidad por enfermedad de Alzheimer en Brasil, 2000 a 2019 / Trends in mortality from Alzheimer's disease in Brazil, 2000-2019

Objetivo: analisar as tendências das taxas de mortalidade por doença de Alzheimer no Brasil e nas suas macrorregiões, por faixa etária e sexo, no período de 2000 a 2019. Métodos: estudo de séries temporais sobre mortalidade por doença de Alzheimer no Brasil e suas macrorregiões por faixa etária e sexo; os dados foram extraídos do Sistema de Informação sobre Mortalidade (SIM); o modelo de Prais-Winsten foi utilizado para análise das tendências. Resultados: houve 211.658 óbitos no período analisado, com tendência crescente na mortalidade por doença de Alzheimer no país em idosos de 60-69 anos (VPA = 4,3; IC95% 2,9;5,9), 70-79 anos (VPA = 8,1; IC95% 4,8;11,5) e ≥ 80 anos (VPA = 11,3; IC95% 8,1;14,6), e em todas as macrorregiões, faixas etárias e sexo. Conclusão: o Brasil e todas as suas macrorregiões apresentaram tendência crescente nas taxas de mortalidade por doença de Alzheimer, seguindo a tendência mundial.

Objective: to analyze trends in mortality rates due to Alzheimer's disease in Brazil and its macro-regions by age and sex, from 2000 to 2019. Methods: this was a time-series study on mortality from Alzheimer's disease in Brazil and its macro-regions by age and sex; data were obtained from the Mortality Information System; a Prais-Winsten model was used to analyze trends. Results: there were 211,658 deaths in the period analyzed, with an increasing trend in Alzheimer's disease mortality in Brazil in elderly people aged 60-69 years (APC = 4.3; 95%CI 2.9;5.9), 70-79 years (APC = 8.1; 95%CI 4.8;11.5) and ≥ 80 years (APC = 11.3; 95%CI 8.1;14.6) and in all macro-regions, age groups and sexes. Conclusion: Brazil and all its macro-regions showed a rising trend in Alzheimer's disease mortality rates, following the global trend.

Objetivo: analizar las tendencias en las tasas de mortalidad por enfermedad de Alzheimer en Brasil y sus macrorregiones por grupo de edad y sexo, de 2000 a 2019. Métodos: estudio de series temporales de mortalidad por enfermedad de Alzheimer en Brasil y sus macrorregiones por grupo de edad y sexo; los datos se obtuvieron del Sistema de Información sobre Mortalidad del Ministerio de Salud de Brasil; se utilizó el modelo Prais-Winsten para analizar tendencias. Resultados: hubo 211.658 óbitos, con tendencia creciente en la mortalidad por enfermedad de Alzheimer en el país, en adultos mayores de 60-69 años (VPA = 4,3; IC95% 2,9;5,9), 70-79 años (VPA = 8,1; IC95%: 4,8;11,5) y ≥ 80 años (VPA = 11,3; IC95% 8,1;14,6) y en todas las macrorregiones, grupos de edad y sexo. Conclusión: Brasil y todas sus macrorregiones mostraron una tendencia creciente en las tasas de mortalidad por enfermedad de Alzheimer siguiendo la tendencia mundial.

Una vista a la tasa de mortalidad por enfermedad de alzheimer en Chile en el periodo de 2017 a 2021 / A view of the mortality rate due to alzheimer's disease in Chile in the period from 2017 to 2021

Introducción: La enfermedad de Alzheimer (EA) es la principal causa de demencia, caracterizada por pérdida progresiva de memoria. Principal fuente de morbimortalidad en mayores de 65 años. En los últimos 20 años las muertes por EA han aumentado un 145% en el mundo. En Chile no hay estudios actuales que describan mortalidad por EA. El objetivo del presente trabajo es analizar y comparar las tasas de mortalidad (TM) por EA según sexo y grupo etario en Chile entre 2017-2021. Materiales y métodos: Estudio descriptivo, ecológico, sobre defunciones por EA entre 2017-2021 en Chile según sexo y grupo etario (n=10.223). Información obtenida de la base de datos del Departamento de Estadísticas e Información de Salud. Se realizó estadística descriptiva y cálculo de TM. No se requiere comité de ética. Resultados: La máxima TM del periodo fue 11,74 por cada 100.000 habitantes en 2021. El sexo femenino logró la mayor TM en este periodo. El grupo etario con mayor cantidad de defunciones fue el de 81 o más años con 76.6% (7.829) de las defunciones totales. Discusión: Se evidenció mantención y luego ascenso de TM por EA, podría deberse al aumento en la esperanza de vida. La mayor frecuencia de defunciones según sexo y edad, podría explicarse por mayor vulnerabilidad femenina a desarrollar EA y a cambios fisiológicos del envejecimiento. En conclusión, la TM por EA en Chile ha aumentado, probablemente secundario al aumento en la esperanza de vida. Se hace un llamado a continuar el estudio de la patología.

Introduction: Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive memory loss. It is the main source of morbidity and mortality in individuals over 65 years of age, with age being its primary non-modifiable risk factor. In the last 20 years, deaths from AD have increased by 145% worldwide. However, there are no current studies in Chile that describe mortality from AD. The objective of this study is to analyze and compare mortality rates due to AD according to sex and age group in the Chilean population during the years 2017-2021. Material and Methods: Descriptive, ecological study on deaths from AD between 2017-2021 in Chile, categorized by sex and age group (n=10,223). The database was obtained from the Department of Health Statistics and Information. Descriptive statistics and mortality rate calculations were performed. No ethics committee approval was required. Results: The maximum mortality rate (MR) was observed in 2021 with a value of 11.74 per 100,000 inhabitants. Women had the highest MR in this period. The age group with the highest number of deaths was 81 years or older, accounting for 76.6% (7,829) of the total deaths. Discussion: A plateau and subsequent increase in MR due to AD were observed, possibly explained by the increase in life expectancy. The higher frequency of deaths in women and specific age groups may be attributed to the higher vulnerability of women to developing AD and physiological changes related to aging. In conclusion, the MR from AD has increased in Chile, likely due to the rise in life expectancy, emphasizing the importance of continued research on this pathology.

COVID-19 Case Fatality and Alzheimer's Disease.

Previous studies have identified dementia as a risk factor for death from coronavirus disease 2019 (COVID-19). However, it is unclear whether Alzheimer's disease (AD) is an independent risk factor for COVID-19 case fatality rate. In a retrospective cohort study, we identified 387,841 COVID-19 patients through TriNetX. After adjusting for demographics and comorbidities, we found that AD patients had higher odds of dying from COVID-19 compared to patients without AD (Odds Ratio: 1.20, 95%confidence interval: 1.09-1.32, p < 0.001). Interestingly, we did not observe increased mortality from COVID-19 among patients with vascular dementia. These data are relevant to the evolving COVID-19 pandemic.

Methods to Analyse Time-to-Event Data: The Kaplan-Meier Survival Curve.

Studies performed in the field of oxidative medicine and cellular longevity frequently focus on the association between biomarkers of cellular and molecular mechanisms of oxidative stress as well as of aging, immune function, and vascular biology with specific time to event data, such as mortality and organ failure. Indeed, time-to-event analysis is one of the most important methodologies used in clinical and epidemiological research to address etiological and prognostic hypotheses. Survival data require adequate methods of analyses. Among these, the Kaplan-Meier analysis is the most used one in both observational and interventional studies. In this paper, we describe the mathematical background of this technique and the concept of censoring (right censoring, interval censoring, and left censoring) and report some examples demonstrating how to construct a Kaplan-Meier survival curve and how to apply this method to provide an answer to specific research questions.

Telephone Interview for Cognitive Status Scores Associate with Cognitive Impairment and Alzheimer's Disease Pathology at Death.

BACKGROUND: Early diagnosis of Alzheimer's disease (AD) provides an opportunity for early intervention. Cognitive testing has proven to be a reliable way to identify individuals who may be at risk of AD. The Telephone Assessment for Cognitive Screening (TICS) is proficient in screening for cognitive impairment. However, its ability to identify those at risk of developing AD pathology is unknown. OBJECTIVE: We aim to investigate associations between TICS scores, collected over a period of 13 years, and the cognitive status of participants at death. We also examine relationships between TICS scores and neuropathological indices of AD (CERAD score, Thal phase, and Braak stage). METHODS: Between 2004 and 2017, participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age underwent cognitive assessment using TICS. Scores from four time points were available for analysis. Cognitive impairment and AD pathology at death was evaluated in 101 participants. RESULTS: TICS scores at time points 2, 3, and 4 were significantly lower in those cognitively impaired at death compared to those considered cognitively normal. There were significant negative correlations between TICS scores and CERAD score and Braak stage at time points 2 and 4. No correlations between Thal phase and TICS were found. CONCLUSION: Findings indicate that TICS could be used not only to screen for cognitive impairment, but also to identify individuals at risk of developing AD pathology, many years before any overt symptoms occur. Once identified, 'at risk' individuals could be targeted for early interventions which could attenuate the progression of the disease.

Chocolate consumption and all-cause and cause-specific mortality in a US population: a post hoc analysis of the PLCO cancer screening trial.

Few studies with mixed results have examined the association between chocolate consumption and mortality. We aimed to examine this association in a US population. A population-based cohort of 91891 participants aged 55 to 74 years was identified. Chocolate consumption was assessed via a food frequency questionnaire. Cox regression was used to estimate risk estimates. After an average follow-up of 13.5 years, 19586 all-cause deaths were documented. Compared with no regular chocolate consumption, the maximally adjusted hazard ratios of all-cause mortality were 0.89 [95% confidence interval (CI) 0.84-0.94], 0.84 (95% CI 0.79-0.90), 0.86 (95% CI 0.81-0.93), and 0.87 (95% CI 0.82-0.93) for >0-0.5 servings/week, >0.5-1 serving/week, >1-2 servings/week, and >2 servings/week, respectively (Ptrend = 0.009). A somewhat stronger inverse association was observed for mortality from cardiovascular disease and Alzheimer's disease. A nonlinear dose-response pattern was found for all-cause and cardiovascular mortality (all Pnonlinearity < 0.01), with the lowest risk observed at chocolate consumption of 0.7 servings/week and 0.6 servings/week, respectively. The favorable associations with all-cause and cardiovascular mortality were found to be more pronounced in never smokers than in current or former smokers (all Pinteraction < 0.05). In conclusion, chocolate consumption confers reduced risks of mortality from all causes, cardiovascular disease, and Alzheimer's disease in this US population.

The Burden of Alzheimer's Disease Mortality in the United States, 1999-2018.

BACKGROUND: The increasing prevalence of Alzheimer's disease (AD), along with the associated burden on healthcare systems, presents a substantial public health challenge. OBJECTIVE: This study aimed to investigate trends in AD mortality and the relevant burden across the United States (U.S.) from 1999 to 2018 and to predict mortality trends between 2019 and 2023. METHODS: Data on AD-related deaths between 1999 and 2018 were collected from the WONDER database administered by the U.S. Centers for Disease Control and Prevention (CDC). The Joinpoint Regression Program was used to analyze mortality trends due to AD. Years of life lost (YLL) were calculated to explore the burden of AD deaths. An autoregressive integrated moving average (ARIMA) model was employed to forecast mortality trends from 2019 to 2023. RESULTS: Over a recent 20-year period, the number of AD deaths in the U.S. increased from 44,536 (31,145 females and 13,391 males) to 122,019 (84,062 females and 37,957 males). The overall age-adjusted mortality rate increased from 16.5/100,000 in 1999 to 30.5/100,000 in 2018. AD mortality is projected to reach 42.40/100000 within the year 2023. Overall, AD resulted in 322,773.00 YLL (2.33 per 1000 population) in 1999 and 658,501.87 YLL (3.68 per 1000 population) in 2018. CONCLUSION: Our findings demonstrate an increase in AD mortality in the U.S. from 1999 to 2018 as well as a rapid increase from 2019 to 2023. The high burden of AD deaths emphasizes the need for targeted prevention, early diagnosis, and hierarchical management.

Geographic disparities in mortality from Alzheimer's disease and related dementias.

OBJECTIVES: The regions with highest and lowest Alzheimer's disease (AD) mortality across the United States at state/county levels were identified and their contribution to the differences in total mortality rates between these regions was evaluated. The disease, disease group, sex, race/ethnicity, and place-of-death-related inter-region differences that engender the disparity in mortality were quantitatively described. The hypothesis that inter-regional differences in filling out death certificates are a major contributor to differences in AD mortality was tested. DESIGN: Retrospective evaluation of death certificate data. SETTING: The United States. PARTICIPANTS: Deceased US residents, 1999-2018. METHODS: Region-specific age-adjusted mortality rates and group-specific rate decomposition. RESULTS: The county clusters with the highest and lowest AD mortality rates were in Washington (WA) and New York (NY), respectively, with other notable high-mortality clusters on the border of Tennessee, Georgia, and Alabama as well as in North Dakota and South Dakota. These patterns were stable over the 1999-2018 period. AD had the highest contribution to total mortality difference between WA and NY (156%, higher in WA), in contrast circulatory diseases had a contribution of comparable magnitude (154%) but were higher in NY. Differences in cause-of-death certificate coding, either through coding of non-AD dementias, or other conditions accompanying a potential AD death could not account for differences in AD mortality between NY and WA. CONCLUSIONS: Inter-regional differences in filling out death certificates were not a major contributor to variation in AD mortality between the regions with the highest and lowest rates. The respective mitigation of the effects of neural and circulatory diseases and several other high-impact conditions would not negate the disparity in mortality between NY and WA.